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一种新型免疫策略产生的 pan 特异性抗血清对神经毒性蛇毒表现出广谱的中和作用。

A pan-specific antiserum produced by a novel immunization strategy shows a high spectrum of neutralization against neurotoxic snake venoms.

机构信息

Department of Microbiology, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok, 10400, Thailand.

Laboratory of Immunology, Chulabhorn Research Institute, Bangkok, 10210, Thailand.

出版信息

Sci Rep. 2020 Jul 9;10(1):11261. doi: 10.1038/s41598-020-66657-8.

Abstract

Snakebite envenomation is a neglected tropical disease of high mortality and morbidity largely due to insufficient supply of effective and affordable antivenoms. Snake antivenoms are mostly effective against the venoms used in their production. It is thus crucial that effective and affordable antivenom(s) with wide para-specificity, capable of neutralizing the venoms of a large number of snakes, be produced. Here we studied the pan-specific antiserum prepared previously by a novel immunization strategy involving the exposure of horses to a 'diverse toxin repertoire' consisting of 12 neurotoxic Asian snake toxin fractions/ venoms from six species. This antiserum was previously shown to exhibit wide para-specificity by neutralizing 11 homologous and 16 heterologous venoms from Asia and Africa. We now show that the antiserum can neutralize 9 out of 10 additional neurotoxic venoms. Altogether, 36 snake venoms belonging to 10 genera from 4 continents were neutralized by the antiserum. Toxin profiles previously generated using proteomic techniques of these 36 venoms identified α-neurotoxins, β-neurotoxins, and cytotoxins as predominant toxins presumably neutralized by the antiserum. The bases for the wide para-specificity of the antiserum are discussed. These findings indicate that it is feasible to generate antivenoms of wide para-specificity against elapid neurotoxic venoms from different regions in the world and raises the possibility of a universal neurotoxic antivenom. This should reduce the mortality resulting from neurotoxic snakebite envenomation.

摘要

蛇伤中毒是一种被忽视的热带病,具有较高的死亡率和发病率,主要原因是有效且负担得起的抗蛇毒血清供应不足。蛇抗蛇毒血清主要对其生产中使用的毒液有效。因此,至关重要的是要生产出具有广泛的同种异型特异性、能够中和大量蛇类毒液的有效且负担得起的抗蛇毒血清。在这里,我们研究了以前通过一种新的免疫策略制备的泛特异性抗血清,该策略涉及将马暴露于由 12 种神经毒性亚洲蛇毒素组分/来自六种物种的毒液组成的“多样化毒素库”中。该抗血清以前显示出广泛的同种异型特异性,可中和来自亚洲和非洲的 11 种同源和 16 种异源毒液。我们现在表明,该抗血清可以中和另外 9 种神经毒性毒液。总共,该抗血清中和了来自 4 个大陆的 10 个属的 36 种蛇毒液。以前使用这些 36 种毒液的蛋白质组学技术生成的毒素图谱确定了α-神经毒素、β-神经毒素和细胞毒素作为抗血清可能中和的主要毒素。讨论了抗血清广泛同种异型特异性的基础。这些发现表明,从世界不同地区产生针对眼镜蛇科神经毒性毒液的广泛同种异型特异性抗蛇毒血清是可行的,并提出了产生通用神经毒性抗蛇毒血清的可能性。这应该会降低因神经毒性蛇伤中毒而导致的死亡率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25b0/7347863/3cd5e2f7e79b/41598_2020_66657_Fig1_HTML.jpg

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